JP2003524634A - ノシセプチン受容体親和性を有するベンズイミダゾール化合物 - Google Patents
ノシセプチン受容体親和性を有するベンズイミダゾール化合物Info
- Publication number
- JP2003524634A JP2003524634A JP2001541507A JP2001541507A JP2003524634A JP 2003524634 A JP2003524634 A JP 2003524634A JP 2001541507 A JP2001541507 A JP 2001541507A JP 2001541507 A JP2001541507 A JP 2001541507A JP 2003524634 A JP2003524634 A JP 2003524634A
- Authority
- JP
- Japan
- Prior art keywords
- dihydro
- piperidinyl
- oxo
- ethyl
- benzamido
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
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- 239000000499 gel Substances 0.000 description 1
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
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- 230000007062 hydrolysis Effects 0.000 description 1
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- FQXXSQDCDRQNQE-UHFFFAOYSA-N markiertes Thebain Natural products COC1=CC=C2C(N(CC3)C)CC4=CC=C(OC)C5=C4C23C1O5 FQXXSQDCDRQNQE-UHFFFAOYSA-N 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16939499P | 1999-12-06 | 1999-12-06 | |
| US60/169,394 | 1999-12-06 | ||
| PCT/US2000/033019 WO2001039775A1 (en) | 1999-12-06 | 2000-12-06 | Benzimidazole compounds having nociceptin receptor affinity |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2007158916A Division JP2007277257A (ja) | 1999-12-06 | 2007-06-15 | ノシセプチン受容体親和性を有するベンズイミダゾール化合物 |
Publications (1)
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|---|---|
| JP2003524634A true JP2003524634A (ja) | 2003-08-19 |
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| JP2001541507A Pending JP2003524634A (ja) | 1999-12-06 | 2000-12-06 | ノシセプチン受容体親和性を有するベンズイミダゾール化合物 |
| JP2007158916A Pending JP2007277257A (ja) | 1999-12-06 | 2007-06-15 | ノシセプチン受容体親和性を有するベンズイミダゾール化合物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007158916A Pending JP2007277257A (ja) | 1999-12-06 | 2007-06-15 | ノシセプチン受容体親和性を有するベンズイミダゾール化合物 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7456198B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1242085B1 (cg-RX-API-DMAC7.html) |
| JP (2) | JP2003524634A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE302770T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU1816901A (cg-RX-API-DMAC7.html) |
| DE (1) | DE60022226D1 (cg-RX-API-DMAC7.html) |
| HK (1) | HK1049284B (cg-RX-API-DMAC7.html) |
| WO (1) | WO2001039775A1 (cg-RX-API-DMAC7.html) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007277257A (ja) * | 1999-12-06 | 2007-10-25 | Euro-Celtique Sa | ノシセプチン受容体親和性を有するベンズイミダゾール化合物 |
| WO2008105497A1 (ja) * | 2007-03-01 | 2008-09-04 | Mitsubishi Tanabe Pharma Corporation | ベンゾイミダゾール化合物およびその医薬用途 |
| JP2014040467A (ja) * | 2007-01-16 | 2014-03-06 | Purdue Pharma Lp | 複素環置換ピペリジン化合物とその使用 |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL158484A0 (en) * | 2001-04-18 | 2004-05-12 | Euro Celtique Sa | Nociceptin analogs |
| CA2465328C (en) * | 2001-11-01 | 2011-06-14 | Michael Francis Gross | Piperidines |
| JP4056977B2 (ja) | 2002-03-29 | 2008-03-05 | 田辺三菱製薬株式会社 | 睡眠障害治療薬 |
| JP2005289816A (ja) * | 2002-05-14 | 2005-10-20 | Banyu Pharmaceut Co Ltd | ベンズイミダゾール誘導体 |
| DE10252666A1 (de) * | 2002-11-11 | 2004-08-05 | Grünenthal GmbH | N-Piperidyl-cyclohexan-Derivate |
| US7202259B2 (en) * | 2002-11-18 | 2007-04-10 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
| AR045939A1 (es) | 2003-09-25 | 2005-11-16 | Solvay Pharm Bv | Derivados de bencimidazolona y quinazolinona como agonistas de los receptores orl 1 humanos |
| AR045843A1 (es) | 2003-10-03 | 2005-11-16 | Solvay Pharm Bv | Derivados de bencimidazolonas y quinazolinonas sustituidas con hidronopol como agonistas en receptores orl 1 humanos |
| KR100886002B1 (ko) | 2004-01-30 | 2009-03-03 | 유로-셀띠끄 소시에떼 아노님 | 4-테트라졸릴-4-페닐피페리딘 화합물의 제조방법 |
| UA83919C2 (en) * | 2004-04-20 | 2008-08-26 | Санофи Авентис | Polymorphic forms of methyl(+)-(s)-alpha-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4h) acetate hydrobromide, clopidrogel hydrobromide |
| US7300947B2 (en) * | 2005-07-13 | 2007-11-27 | Banyu Pharmaceutical Co., Ltd. | N-dihydroxyalkyl-substituted 2-oxo-imidazole derivatives |
| AR054816A1 (es) * | 2005-07-13 | 2007-07-18 | Banyu Pharma Co Ltd | Derivados de n-dihidroxialquil 2-oxo- imidazol sustituidos |
| WO2007037513A1 (ja) * | 2005-09-30 | 2007-04-05 | Banyu Pharmaceutical Co., Ltd. | アリール置換含窒素複素環化合物 |
| US20080015214A1 (en) * | 2005-10-24 | 2008-01-17 | Bignan Gilles C | 3-piperidin-4-yl-indole orl-1 receptor modulators |
| JP2009525269A (ja) * | 2006-01-30 | 2009-07-09 | ユーロ−セルティーク エス．エイ． | カルシウムチャネルブロッカーとしての環状尿素化合物 |
| GB0605784D0 (en) * | 2006-03-22 | 2006-05-03 | Glaxo Group Ltd | Compounds |
| GB0605786D0 (en) * | 2006-03-22 | 2006-05-03 | Glaxo Group Ltd | Compounds |
| US8775704B2 (en) * | 2006-04-05 | 2014-07-08 | Nvidia Corporation | Method and system for communication between a secondary processor and an auxiliary display subsystem of a notebook |
| DE102006046745A1 (de) * | 2006-09-29 | 2008-04-03 | Grünenthal GmbH | Gemischte ORL1/µ-Agonisten zur Behandlung von Schmerz |
| RU2451017C2 (ru) * | 2007-03-01 | 2012-05-20 | Мицубиси Танабе Фарма Корпорейшн | Бензимидазольное соединение и его фармацевтическое применение |
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| WO2009124883A1 (en) * | 2008-04-09 | 2009-10-15 | H. Lundbeck A/S | Novel 1,3-dihydro-benzoimidazol-2-ones as m1 agonists |
| KR101333660B1 (ko) | 2008-07-21 | 2013-11-27 | 시오노기세이야쿠가부시키가이샤 | 치환-퀴녹살린-형 가교-피페리딘 화합물 및 그의 용도 |
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| US20240287019A1 (en) * | 2021-06-07 | 2024-08-29 | Kinki University | T-type calcium channel blocker |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3196157A (en) * | 1962-06-13 | 1965-07-20 | Res Lab Dr C Janssen N V | Benzimidazolinyl piperidines |
| US3318900A (en) * | 1964-05-06 | 1967-05-09 | Janssen Pharmaceutica Nv | Derivatives of benzimidazolinyl piperidine |
| JPS5517385A (en) * | 1978-07-20 | 1980-02-06 | Science Union & Cie | Benzimidazolinone derivative and medical composition containing it |
| US4329353A (en) * | 1980-10-22 | 1982-05-11 | Janssen Pharmaceutica, N.V. | 1-(4-Aryl-cyclohexyl)piperidine derivatives, method of use thereof and pharmaceutical compositions thereof |
| WO1997040035A1 (en) * | 1996-04-19 | 1997-10-30 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
| WO1998054168A1 (en) * | 1997-05-30 | 1998-12-03 | Banyu Pharmaceutical Co., Ltd. | 2-oxoimidazole derivatives |
| WO1999036421A1 (en) * | 1998-01-19 | 1999-07-22 | Pfizer Pharmaceuticals Inc. | 4-(2-keto-1-benzimidazolinyl)piperidine compounds as orl1-receptor agonists |
| JP2002521472A (ja) * | 1998-07-27 | 2002-07-16 | シェーリング コーポレイション | ノシセプチンレセプターｏｒｌ−１に対する高親和性リガンド |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3161645A (en) | 1962-12-18 | 1964-12-15 | Res Lab Dr C Janssen N V | 1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds |
| JPS58180481A (ja) | 1982-04-15 | 1983-10-21 | Kyowa Hakko Kogyo Co Ltd | 新規なピペリジン誘導体 |
| EP0974583B1 (en) | 1995-09-13 | 2002-05-29 | Kyowa Hakko Kogyo Co., Ltd. | Phenylpiperidine derivatives |
| SI0921125T1 (en) | 1997-12-05 | 2002-04-30 | F. Hoffmann-La Roche Ag | 1,3,8-Triazaspiro(4,5)decan-4-on derivatives |
| US6166209A (en) | 1997-12-11 | 2000-12-26 | Hoffmann-La Roche Inc. | Piperidine derivatives |
| US6626939B1 (en) | 1997-12-18 | 2003-09-30 | Boston Scientific Scimed, Inc. | Stent-graft with bioabsorbable structural support |
| NZ507760A (en) | 1998-03-26 | 2002-10-25 | Japan Tobacco Inc | Amide derivatives and nociceptin antagonists |
| AU3809999A (en) | 1998-05-18 | 1999-12-06 | Novo Nordisk A/S | Novel 1,3,8-triazaspiro[4.5]decanones with high affinity for opioid receptor subtypes |
| US6262066B1 (en) * | 1998-07-27 | 2001-07-17 | Schering Corporation | High affinity ligands for nociceptin receptor ORL-1 |
| AU1816901A (en) * | 1999-12-06 | 2001-06-12 | Euro-Celtique S.A. | Benzimidazole compounds having nociceptin receptor affinity |
-
2000
- 2000-12-06 AU AU18169/01A patent/AU1816901A/en not_active Abandoned
- 2000-12-06 JP JP2001541507A patent/JP2003524634A/ja active Pending
- 2000-12-06 US US09/730,934 patent/US7456198B2/en not_active Expired - Lifetime
- 2000-12-06 EP EP00980981A patent/EP1242085B1/en not_active Expired - Lifetime
- 2000-12-06 HK HK03101335.9A patent/HK1049284B/en not_active IP Right Cessation
- 2000-12-06 WO PCT/US2000/033019 patent/WO2001039775A1/en not_active Ceased
- 2000-12-06 AT AT00980981T patent/ATE302770T1/de not_active IP Right Cessation
- 2000-12-06 DE DE60022226T patent/DE60022226D1/de not_active Expired - Lifetime
-
2006
- 2006-07-28 US US11/494,826 patent/US7678809B2/en not_active Expired - Fee Related
-
2007
- 2007-06-15 JP JP2007158916A patent/JP2007277257A/ja active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3196157A (en) * | 1962-06-13 | 1965-07-20 | Res Lab Dr C Janssen N V | Benzimidazolinyl piperidines |
| US3318900A (en) * | 1964-05-06 | 1967-05-09 | Janssen Pharmaceutica Nv | Derivatives of benzimidazolinyl piperidine |
| JPS5517385A (en) * | 1978-07-20 | 1980-02-06 | Science Union & Cie | Benzimidazolinone derivative and medical composition containing it |
| US4329353A (en) * | 1980-10-22 | 1982-05-11 | Janssen Pharmaceutica, N.V. | 1-(4-Aryl-cyclohexyl)piperidine derivatives, method of use thereof and pharmaceutical compositions thereof |
| WO1997040035A1 (en) * | 1996-04-19 | 1997-10-30 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
| WO1998054168A1 (en) * | 1997-05-30 | 1998-12-03 | Banyu Pharmaceutical Co., Ltd. | 2-oxoimidazole derivatives |
| WO1999036421A1 (en) * | 1998-01-19 | 1999-07-22 | Pfizer Pharmaceuticals Inc. | 4-(2-keto-1-benzimidazolinyl)piperidine compounds as orl1-receptor agonists |
| JP2002521472A (ja) * | 1998-07-27 | 2002-07-16 | シェーリング コーポレイション | ノシセプチンレセプターｏｒｌ−１に対する高親和性リガンド |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007277257A (ja) * | 1999-12-06 | 2007-10-25 | Euro-Celtique Sa | ノシセプチン受容体親和性を有するベンズイミダゾール化合物 |
| JP2014040467A (ja) * | 2007-01-16 | 2014-03-06 | Purdue Pharma Lp | 複素環置換ピペリジン化合物とその使用 |
| WO2008105497A1 (ja) * | 2007-03-01 | 2008-09-04 | Mitsubishi Tanabe Pharma Corporation | ベンゾイミダゾール化合物およびその医薬用途 |
| JP5313865B2 (ja) * | 2007-03-01 | 2013-10-09 | 田辺三菱製薬株式会社 | ベンゾイミダゾール化合物およびその医薬用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| DE60022226D1 (de) | 2005-09-29 |
| EP1242085B1 (en) | 2005-08-24 |
| JP2007277257A (ja) | 2007-10-25 |
| ATE302770T1 (de) | 2005-09-15 |
| WO2001039775A1 (en) | 2001-06-07 |
| US7456198B2 (en) | 2008-11-25 |
| EP1242085A1 (en) | 2002-09-25 |
| US20060264638A1 (en) | 2006-11-23 |
| EP1242085A4 (en) | 2003-02-12 |
| HK1049284A1 (en) | 2003-05-09 |
| US20020128288A1 (en) | 2002-09-12 |
| HK1049284B (en) | 2006-02-24 |
| AU1816901A (en) | 2001-06-12 |
| US7678809B2 (en) | 2010-03-16 |
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